The present invention relates to improving therapy and drug tailoring in oncology patients, and, more particularly to improving the reliability of computed tomography (“CT”) examinations measuring the effectiveness of the drug treatment in reducing cancerous tissue.
More than 15 million follow-up examinations are performed annually to monitor cancer treatment in the West. The main imaging modalities are CT, MRI and PET/CT. MRIs and PET/CT are the most sensitive in detection but have drawbacks regarding their large scale use for the millions affected. These drawbacks include (i) a limited number of equipment (ii) long and uncomfortable examination time and (iii) very expensive to use. CT machines, although less sensitive for functional changes, have the advantage of being relatively cost-effective, not complicated, requiring only short examination time and there are a large number of available scanners.
Conventional CT blood perfusion studies employ CT examinations on two different dates (the first date being before the drug treatment was initiated) and calculate a rate of reduction in blood perfusion between the two dates. Since cancerous cells have a much higher blood supply, called neovascularization, they are assumed to have a proportionately higher rate of blood perfusion.
The blood perfusion measured by CT scanners has severe reliability problems. Blood perfusion may be measured by detecting presence of contrast material pixel by pixel as the contrast material, such as iodine, flows through the cancerous tissue. FIG. 1 is a perfusion curve showing a combination of two curves, (i) wash-in of blood containing contrast material increasing exponentially and (ii) wash-out of this blood containing contrast material decreasing logarithmically. As is known, the actual perfusion, C, the maximum attenuation point may be very sensitive to changes in A and B and this makes it a good measure to represent changes in overall perfusion in the tissue. Techniques for calculating perfusion include the deconvolusion technique and the maximal slope technique. However, the variables obtained with either technique may be influenced by external and internal factors not reflecting changes in the true tissue perfusion rate. Accordingly, when the perfusion rate may be re-measured at the second CT examination, factors that are unrelated to the true tissue perfusion and hence also unrelated to the value of the drug or treatment, distort the comparison of blood perfusion values required to perform drug tailoring.
The factors influencing the maximum attenuation point include external factors such as injection rate, contract dose and concentration, machine calibration, stability of the x-ray tube, and more. GE, Phillips, Toshiba and Siemens make most of the CT machines sold today. Each of these different manufacturers employs different algorithms and methods to calculate the blood perfusion result from the imaging data obtained during the CT examination. Since the second CT examination may be performed by a different machine, the results will be unreliable.
Internal factors also contribute to variability of CT exam blood perfusion readings. During the first examination, the patient's heart rate may have been 60 and during the second examination the same patient's heart rate may have been 70. Similarly, the patient may have been dehydrated during only one of the examinations. Both of these facts affect blood perfusion results. Other internal factors may include aortic insufficiency, cardiac output variability, the patient's general metabolic status and other patient related changes. In addition, a 6% change in the calibration of HU of water may be observed even within a period of minutes.
One way that the prior art CT examinations have attempted to deal with the variability that distorts the results of CT examinations and limits their reliability and usefulness in drug tailoring is by using a control tissue, such as a healthy aorta, that represents the input function of blood. The idea is to scan the healthy aorta at the same time that the cancerous tissue is scanned using the same CT equipment. An underlying assumption is made that blood perfusion in the cancerous tissue, for example in the kidney, will not change from the first examination to the second if no changes were observed in the actual tumorous tissue.
In practice, however, this underlying assumption is incorrect. In fact, there are daily changes in cardiac output, which may cause daily changes in the mathematical relationship (i.e. ratio) between blood perfusion in the cancerous tissue (i.e. liver) and blood perfusion in the healthy tissue (i.e. heart). Accordingly, conventional CT imaging is left with the unreliability caused by the variability associated with the above internal and external factors. Because of the known unreliability, a significant reduction in blood perfusion may be typically required before judging that a drug treatment is effective for a certain patient because it is assumed that some of the observed apparent decrease in blood perfusion of the cancerous tissue may in fact have been caused by factors unrelated to true changes in tissue perfusion. This limits the usefulness of CT examinations in drug tailoring and harms patient outcomes.
There is a compelling need to have an apparatus or method that will significantly improve oncology treatment outcomes, such as by significantly improving the reliability of CT scanners and improve drug tailoring.